Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O=C1C2C(=CC=CC=2)N=C(C(OCC)=O)N1.[Br:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[C:32]3[C:31](=[O:33])[NH:30][C:29]([C:34]([O:36]CC)=O)=[N:28][C:27]=3[S:26][CH:25]=2)=[CH:20][CH:19]=1.C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)N2C=NC(CCCOC3C=C(CN)C=CN=3)=N2)C=CC=CC=1.C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[N:82]2[CH:86]=[N:85][C:84]([O:87][CH2:88][CH2:89][O:90][C:91]3[CH:92]=[C:93]([CH2:97][NH2:98])[CH:94]=[CH:95][CH:96]=3)=[N:83]2)C=CC=CC=1>>[Br:17][C:18]1[CH:19]=[CH:20][C:21]([C:24]2[C:32]3[C:31](=[O:33])[NH:30][C:29]([C:34]([NH:98][CH2:97][C:93]4[CH:94]=[CH:95][CH:96]=[C:91]([O:90][CH2:89][CH2:88][O:87][C:84]5[N:85]=[CH:86][NH:82][N:83]=5)[CH:92]=4)=[O:36])=[N:28][C:27]=3[S:26][CH:25]=2)=[CH:22][CH:23]=1
Reactant: CCOC(=O)c1nc2scc(-c3ccc(Br)cc3)c2c(=O)[nH]1
Reactant: NCc1cccc(OCCOc2ncn(C(c3ccccc3)(c3ccccc3)c3ccccc3)n2)c1
Agent: CCOC(=O)c1nc2ccccc2c(=O)[nH]1
Agent: NCc1ccnc(OCCCc2ncn(C(c3ccccc3)(c3ccccc3)c3ccccc3)n2)c1
Product: O=C(NCc1cccc(OCCOc2nc[nH]n2)c1)c1nc2scc(-c3ccc(Br)cc3)c2c(=O)[nH]1

Procedure:
By a method similar to that in Example 22, and using, instead of ethyl 4-oxo-3,4-dihydro-2-quinazolinecarboxylate, ethyl 5-(4-bromophenyl)-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-2-carboxylate obtained in Reference Example 79 and using, instead of 1-[2-({3-[1-(triphenylmethyl)-1H-1,2,4-triazol-3-yl]propyl}oxy)pyridin-4-yl]methaneamine, 1-{3-[(2-{[1-(triphenylmethyl)-1H-1,2,4-triazol-3-yl]oxy}ethyl)oxy]phenyl}methanamine obtained in Reference Example 32, the title compound was obtained as a white powder (147.7 mg, 71%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[OH:12])[C:5](OC)=[O:6].[NH2:13][NH2:14]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[OH:12])[C:5]([NH:13][NH2:14])=[O:6]
Reactant: COC(=O)c1ccc(O)c(Cl)c1
Reactant: NN
Solvent: CCO
Product: NNC(=O)c1ccc(O)c(Cl)c1
Yield: 60 %

Procedure:
To a sample of methyl 3-chloro-4-hydroxybenzoate (2 g) dissolved in ethanol (50 mL) was added hydrazine (1.8 mL). The reaction was refluxed overnight under nitrogen. Upon cooling the reaction vessel, the desired product crystallized out of solution. The white solid was isolated by filtration. Recrystallization from hot ethanol gave the 3-chloro-4-hydroxybenzoic acid hydrazide in 60% yield.
Reaction SMILES: O.O.[Sn](Cl)(Cl)(Cl)Cl.[N+:8]([C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:22][CH2:21][N:20]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:19][CH2:18]2)=[CH:13][CH:12]=1)([O-])=O>C(O)C>[C:24]1([CH2:23][N:20]2[CH2:19][CH2:18][N:17]([C:14]3[CH:13]=[CH:12][C:11]([NH2:8])=[CH:16][CH:15]=3)[CH2:22][CH2:21]2)[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: O=[N+]([O-])c1ccc(N2CCN(Cc3ccccc3)CC2)cc1
Agent: Cl[Sn](Cl)(Cl)Cl
Solvent: CCO
Solvent: O
Product: Nc1ccc(N2CCN(Cc3ccccc3)CC2)cc1
Temperature: 25 °C

Procedure:
Add 474 g (2.10 mol) tin chloride dihydrate to a refluxing solution of 125 g (0.420 mol) 4-(4-nitrophenyl)-1-(phenylmethyl)piperazine in ethanol. Reflux the solution for about 15 h then cool to room temperature and remove the solvent. Dissolve the residue in water and adjust to pH 12 withsodium hydroxide. Extract the aqueous solution with methylene chloride and dry the organic layer with anhydrous sodium sulfate. Concentration at reduced pressure gives the title compound.
Reaction SMILES: [Cl:1][C:2](=[CH2:10])[C:3]([CH3:9])([CH3:8])[C:4]([O:6]C)=[O:5].[OH-].[Na+]>O>[Cl:1][C:2](=[CH2:10])[C:3]([CH3:9])([CH3:8])[C:4]([OH:6])=[O:5]
Reactant: C=C(Cl)C(C)(C)C(=O)OC
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: C=C(Cl)C(C)(C)C(=O)O
Yield: 44 %

Procedure:
A mixture of methyl 3-chloro-2,2-dimethylbut-3-enoate (42.0 g, 0.26 mol) and NaOH (12.4 g, 0.31 mol) in water (300 mL) was heated at reflux overnight. After cooling, the reaction mixture was extracted with ether. The organic layer contained 20 g of methyl 3-chloro-2,2-dimethylbut-3-enoate (48% recovered). The aqueous layer was acidified with cold 20% HCl solution and was extracted with ether (250 mL×3). The combined organic layers were dried and evaporated under reduced pressure to give 3-chloro-2,2-dimethylbut-3-enoic acid (17 g, 44%), which was used directly in the next step.
Reaction SMILES: [F:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH:4]=O.Cl.[NH2:12][OH:13].[OH-].[Na+].C(O)C>O>[F:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH:4]=[N:12][OH:13]
Reactant: O=Cc1ccc(F)cc1F
Reactant: NO
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: ON=Cc1ccc(F)cc1F
Yield: 83.5 %

Procedure:
In a fashion similar to that for preparation 13, 2,4-difluorobenzaldehyde (5.00 g, 35.2 mmol), hydroxylamine hydrochloride (2.94 g, 42.3 mmol), NaOH (7.04 g, 88.0 mmol; as a 50% solution by weight in water), ethanol (15 ml), H2O (15 ml), and ice (30 g) gave 2,4-difluorobenzaldehyde oxime (4.62 g, 84%) which was used without purification.
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@H:12]([CH2:31][O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[O:11][C@H:10]1[C:40]1[C:48]2[C:43](=[C:44]([CH3:49])[CH:45]=[CH:46][CH:47]=2)[NH:42][CH:41]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:53][C:54]1[CH:63]=[CH:62][C:57]([C:58]([O:60][CH3:61])=[O:59])=[CH:56][CH:55]=1.Cl>CN(C)C=O>[CH2:1]([O:8][C@@H:9]1[C@@H:14]([O:15][CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@H:12]([CH2:31][O:32][CH2:33][C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[O:11][C@H:10]1[C:40]1[C:48]2[C:43](=[C:44]([CH3:49])[CH:45]=[CH:46][CH:47]=2)[N:42]([CH2:53][C:54]2[CH:55]=[CH:56][C:57]([C:58]([O:60][CH3:61])=[O:59])=[CH:62][CH:63]=2)[CH:41]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1cccc2c([C@@H]3O[C@H](COCc4ccccc4)[C@@H](OCc4ccccc4)[C@H](OCc4ccccc4)[C@H]3OCc3ccccc3)c[nH]c12
Reactant: COC(=O)c1ccc(CBr)cc1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(Cn2cc([C@@H]3O[C@H](COCc4ccccc4)[C@@H](OCc4ccccc4)[C@H](OCc4ccccc4)[C@H]3OCc3ccccc3)c3cccc(C)c32)cc1
Reaction time: 0.25 h
Yield: 93.2 %

Procedure:
To a solution of 3-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-7-methyl-1H-indole (0.28 g) in N,N-dimethyl-formamide (4 mL) was added 55% sodium hydride (22 mg) under ice-cooling, and the mixture was stirred at the same temperature for 15 minutes. To this mixture was added methyl 4-(bromo-methyl)benzoate (0.12 g) at the same temperature, and the mixture was stirred at the same temperature for 15 minutes, and stirred at room temperature for 1 hour. The reaction mixture was poured into 0.5 mol/L hydrochloric acid, and the resulting mixture was extracted with diethyl ether. The extract was washed with water and brine successively, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=5/1-3/1) to give 3-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-1-[4-(methoxycarbonyl)benzyl]-7-methyl-1H-indole (0.32 g). This material was dissolved in a mixed solvent of ethanol (5 mL) and tetra hydrofuran (2.5 mL). To the solution was added potassium hydroxide (0.45 g), and the mixture was stirred at 50° C. overnight. The reaction mixture was poured into 1 mol/L hydrochloric acid (10 mL), and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine successively, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give the title compound (0.31 g)
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]([C:7]1[CH:12]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[C:15]([F:20])[CH:14]=2)[NH:11][C:10]([O:21][CH3:22])=[N:9][C:8]=1[CH3:23])=[O:6].[CH3:24]I>CN(C=O)C>[CH3:3][O:4][C:5]([C:7]1[CH:12]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[C:15]([F:20])[CH:14]=2)[N:11]([CH3:24])[C:10]([O:21][CH3:22])=[N:9][C:8]=1[CH3:23])=[O:6].[CH3:3][O:4][C:5]([C:7]1[CH:12]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[C:15]([F:20])[CH:14]=2)[N:11]=[C:10]([O:21][CH3:22])[N:9]([CH3:24])[C:8]=1[CH3:23])=[O:6]
Reactant: COC(=O)C1=C(C)N=C(OC)NC1c1ccc(F)c(F)c1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)C1=C(C)N(C)C(OC)=NC1c1ccc(F)c(F)c1
Product: COC(=O)C1=C(C)N=C(OC)N(C)C1c1ccc(F)c(F)c1
Reaction time: 0.5 h

Procedure:
To a suspension of a 60% oil dispersion of NaH (96 mg, 2.2 mmol) in DMF (3 ml) at 0° C. was added a DMF solution (5 ml) of (+6-(3,4-Difluorophenyl)-2-methoxy-4-methyl-1,6-dihydro-pyrimidine-5-carboxylic acid methyl ester (592 mg, 2.0 mmol, [αD]=+28°). After the mixture was stirred 30 min, a DMF solution (2 ml) of methyliodide (312 mg, 2.2 mmol) was added and the reaction stirred at room temperature for 45 min. The DMF was removed in vacuo, the residue treated with water and extracted with ethyl acetate(3X). The extracts were combined, washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo to give a crude oil (800 mg). Flash chromatography on silica gel (3% to 6% diethyl ether in methylene chloride) gave 6-(3,4-difluorophenyl)-2-methoxy-1,4-dimethyl-1,6-dihydro-pyrimidine-5-carboxylic acid methyl ester and 4-(3,4-difluorophenyl)-2-methoxy-1,6-dimethyl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester as colorless oils.
Reaction SMILES: [CH2:1]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13](Br)[CH:14]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:18][CH:19]1[C:23](=[O:24])[CH2:22][CH2:21][O:20]1>>[CH2:1]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:23]3([OH:24])[CH2:22][CH2:21][O:20][CH:19]3[CH3:18])[CH:14]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Brc1ccc2c(c1)CN(Cc1ccccc1)C2
Reactant: CC1OCCC1=O
Product: CC1OCCC1(O)c1ccc2c(c1)CN(Cc1ccccc1)C2

Procedure:
Prepared in analogy to Example A62(b) from 2-benzyl-5-bromo-2,3-dihydro-1H-isoindole (Example A62(a)) and 2-methyltetrahydrofuran-3-one. Brown oil. MS (m/e): 310.4 ([M+H]+, 100%).
Reaction SMILES: [N+]([O-])(O)=O.[Cl:5][C:6]1[CH:7]=[C:8]([NH:12][C:13]([NH2:15])=[NH:14])[CH:9]=[CH:10][CH:11]=1.[OH-].[Na+].CN(C)[CH:20]=[CH:21][C:22]([C:24]1[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=1)=O>C(O)C(C)C>[Cl:5][C:6]1[CH:7]=[C:8]([NH:12][C:13]2[N:15]=[C:22]([C:24]3[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=3)[CH:21]=[CH:20][N:14]=2)[CH:9]=[CH:10][CH:11]=1
Reactant: N=C(N)Nc1cccc(Cl)c1
Reactant: CN(C)C=CC(=O)c1ccncc1
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)CO
Solvent: O=[N+]([O-])O
Product: Clc1cccc(Nc2nccc(-c3ccncc3)n2)c1

Procedure:
2.8 g (12 mmol) of 3-chloro-phenyl-guanidine nitrate and 0.5 g (12 mmol) of sodium hydroxide are added to a suspension of 2.0 g (11.7 mmol) of 3-dimethylamino-1-(4-pyridyl)-2-propen-1-one [described in EP-A-0 233 461] in 100 ml of isobutanol and the reaction mixture is boiled under reflux for 5 hours. After cooling, the reaction product is isolated by filtration, washed with water and chromatographed (tetrahydrofuran). After crystallisation (tetrahydrofuran/diethyl ether), N-(3-chloro-phenyl)-4-pyridyl-2-pyrimidineamine is obtained; m.p. 167°-168°, Rf =0.38 (methylene chloride:methanol=9:1).
Reaction SMILES: C[O:2][C:3](=[O:32])[C:4](=[O:31])[C:5]1[CH:10]=[CH:9][C:8]([S:11][CH2:12][CH2:13][O:14][C:15]2[C:20]([CH3:21])=[CH:19][CH:18]=[CH:17][C:16]=2[CH2:22][O:23][C:24](=[O:30])[C:25]([CH3:29])([CH3:28])[CH2:26][CH3:27])=[CH:7][CH:6]=1.[OH-].[Na+]>CO.O1CCCC1.O>[CH3:28][C:25]([CH3:29])([CH2:26][CH3:27])[C:24](=[O:30])[O:23][CH2:22][C:16]1[CH:17]=[CH:18][CH:19]=[C:20]([CH3:21])[C:15]=1[O:14][CH2:13][CH2:12][S:11][C:8]1[CH:9]=[CH:10][C:5]([C:4](=[O:31])[C:3]([OH:32])=[O:2])=[CH:6][CH:7]=1
Reactant: CCC(C)(C)C(=O)OCc1cccc(C)c1OCCSc1ccc(C(=O)C(=O)OC)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: CCC(C)(C)C(=O)OCc1cccc(C)c1OCCSc1ccc(C(=O)C(=O)O)cc1

Procedure:
A solution of 4-[[2-[2-[(2,2-dimethyl-1-oxobutoxy)methyl]-6-methylphenoxy]ethyl]thio]-alpha-oxobenzeneacetic acid methyl ester (1.9 g) in warm methanol (10 mL) and tetrahydrofuran (5 mL) was treated with 1N sodium hydroxide (5 mL) and after 10 minutes the mixture was diluted with water and concentrated to remove the organic solvents. The residue was acidified with excess hydrochloric acid and extracted with dichloromethane containing a little tetrahydrofuran. The organic layer was washed with water, dried (Na2SO4), filtered and evaporated to give crude product. Purification was accomplished by chromatography on 60 g of silica gel using dichloromethane-diethyl ether-formic acid (50:50:1) to elute impurities followed by elution with diethyl ether-formic acid (99:1) to recover 1.1 g of pure 4-[[2-[2-[(2,2-dimethyl-1-oxobutoxy) methyl]-6-methylphenoxy]ethyl]thio]-alpha-oxobenzeneacetic acid as a yellow oil.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][C:9]2[CH:28]=[CH:27][C:12]([O:13][CH2:14][C:15]3[N:16]=[C:17](/[CH:20]=[CH:21]/[C:22]4[S:23][CH:24]=[CH:25][CH:26]=4)[O:18][CH:19]=3)=[CH:11][CH:10]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.O1CCCC1>CO>[N:1]1([CH2:6][CH2:7][CH2:8][C:9]2[CH:10]=[CH:11][C:12]([O:13][CH2:14][C:15]3[N:16]=[C:17]([CH2:20][CH2:21][C:22]4[S:23][CH:24]=[CH:25][CH:26]=4)[O:18][CH:19]=3)=[CH:27][CH:28]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: C(=C/c1cccs1)\c1nc(COc2ccc(CCCn3ccnc3)cc2)co1
Solvent: C1CCOC1
Solvent: CO
Product: c1csc(CCc2nc(COc3ccc(CCCn4ccnc4)cc3)co2)c1

Procedure:
A solution of 4-[4-[3-(1-imidazolyl)propyl]phenoxymethyl]-2-[(E)-2-(2-thienyl)ethenyl]oxazole (200 mg) in methanol (10 ml)-tetrahydrofuran (4 ml) was hydrogenated on palladium carbon (10%, wet, 70 mg) at 4 atm. After removal of the catalyst by filtration, the filtrate was concentrated. The hydrogenation was repeated three times to obtain 4-[4-[3-(1-imidazolyl)propyl]phenoxymethyl]-2-[2-(2-thienyl)ethyl]oxazole. Recrystallization from ethyl acetate-methanol gave colorless prisms (155 mg, 79%), mp 68-70° C.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[C:4]([CH3:9])[CH:3]=1.[OH-].[Na+].Cl.Cl[CH2:14][C:15]1[N:16]([CH3:20])[CH:17]=[CH:18][N:19]=1.O>CO>[CH3:9][C:4]1[CH:3]=[C:2]([CH:7]=[CH:6][C:5]=1[S:8][CH2:14][C:15]1[N:16]([CH3:20])[CH:17]=[CH:18][N:19]=1)[NH2:1]
Reactant: Cn1ccnc1CCl
Reactant: Cc1cc(N)ccc1S
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: Cc1cc(N)ccc1SCc1nccn1C
Yield: 90.3 %

Procedure:
To a solution of 4-amino-2-methylthiophenol (500 mg) in methanol (10 ml) was added 1N aqueous solution of sodium hydroxide (12 ml), and a solution of 2-chloromethyl-1-methylimidazole hydrochloride (660 mg) in methanol (10 ml) was added at 0° C. Water was added to the mixture, and the mixture was extracted with ethyl acetate and the organic layer was dried over magnesium sulfate. The solvent was distilled off under reduced pressure and the obtained residue was recrystallized from hexane-ethyl acetate, to give 3-methyl-4-[[(1-methylimidazol-2-yl)methyl]sulfanyl]aniline (757 mg) as crystals.
Reaction SMILES: [NH2:1][C:2]1[N:6]([CH:7]([CH3:17])[CH2:8][CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:5]=[N:4][C:3]=1[C:18]([NH2:20])=[O:19].[C:21]1([CH2:27][C:28](OC)=O)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>>[CH2:27]([C:28]1[NH:20][C:18](=[O:19])[C:3]2[N:4]=[N:5][N:6]([CH:7]([CH3:17])[CH2:8][CH2:9][CH2:10][C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:2]=2[N:1]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: COC(=O)Cc1ccccc1
Reactant: CC(CCCc1ccccc1)n1nnc(C(N)=O)c1N
Product: CC(CCCc1ccccc1)n1nnc2c(=O)[nH]c(Cc3ccccc3)nc21

Procedure:
Analogously to the procedure of Example 1, the title compound is prepared from 566 mg (2 mmol) of 5-amino-1-(1-methyl-4-phenyl-butyl)-1H-[1,2,3]triazole-4-carboxamide and 1.16 g (7.7 mmol) of methyl phenylacetate.
Reaction SMILES: [Si:1]([O:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:11]/[C:10]/1=[CH:34]\[CH:35]=[O:36])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C1(C)C=CC(S([CH2:46][N+:47]#[C-:48])(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+].O>CO>[Si:1]([O:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:11]/[C:10]/1=[CH:34]\[C:35]1[O:36][CH:48]=[N:47][CH:46]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: [C-]#[N+]CS(=O)(=O)c1ccc(C)cc1
Reactant: CC(C)(C)[Si](C)(C)OC1CCN(C(c2ccccc2)(c2ccccc2)c2ccccc2)C/C1=C\C=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: CC(C)(C)[Si](C)(C)OC1CCN(C(c2ccccc2)(c2ccccc2)c2ccccc2)C/C1=C\c1cnco1
Yield: 33.1 %

Procedure:
To a solution of (E)-4-(t-butyldimethylsilyloxy)-3-(formylmethylidene)-1-(triphenylmethyl)piperidine (112 mg) in methanol (2.5 ml) were added successively p-toluenesulfonylmethyl isocyanide (45 mg) and potassium carbonate (32 mg), and the resulting mixture was refluxed for 3.5 hours. After refluxing, water was added to the reaction mixture, and the resulting mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride solution, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column using a mixed solvent of ethyl acetate and hexane (1:19 to 1:3) as the eluent to afford the title compound (40 mg, yield: 32%) as a yellow oil.
Reaction SMILES: Br[C:2]1[CH:17]=[CH:16][C:5]([C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])=[CH:4][C:3]=1[O:18][CH3:19].C[Si](C)(C)[O:22][CH:23]=[C:24]([CH3:26])[CH3:25]>[F-].[F-].[Zn+2].CN(C=O)C>[CH3:19][O:18][C:3]1[CH:4]=[C:5]([CH:16]=[CH:17][C:2]=1[C:24]([CH3:26])([CH3:25])[CH:23]=[O:22])[C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7]
Reactant: COc1cc(C(=O)OCc2ccccc2)ccc1Br
Reactant: CC(C)=CO[Si](C)(C)C
Agent: [F-]
Agent: [Zn+2]
Solvent: CN(C)C=O
Product: COc1cc(C(=O)OCc2ccccc2)ccc1C(C)(C)C=O
Temperature: 80 °C

Procedure:
To a flask purged with nitrogen was added Pd(tBu3P)2 (26 mg, 0.050 mmol), ZnF2 (52 mg, 0.50 mmol) and DMF (4 mL). The reaction mixture was allowed to stir for 10 minutes before benzyl 4-bromo-3-methoxy-benzoate (323 mg, 1.01 mmol) was added followed by trimethyl(2-methylprop-1-enoxy)silane (277 μL, 1.51 mmol). The reaction was heated at 80° C. overnight. The crude mixture was quenched with brine and extracted with EtOAc 3 times. The organic layer was dried over sodium sulfate and the solvent was evaporated to give benzyl 3-methoxy-4-(2-methyl-1-oxopropan-2-yl)benzoate. ESI-MS m/z calc. 312.4, found 313.4 (M+1)+; Retention time: 3.27 minutes (4 min run).
Reaction SMILES: [PH4+].[Li][CH2:3][CH2:4][CH2:5][CH3:6].F[C:8]1[CH:9]=[C:10]([CH:13]=[C:14](OC)[C:15]=1OC)[CH:11]=O.O1C[CH2:23][CH2:22][CH2:21]1>CCCCCC.C(OCC)(=O)C>[C:10]1(/[CH:11]=[CH:6]\[C:5]2[CH:23]=[CH:22][CH:21]=[CH:3][CH:4]=2)[CH:13]=[CH:14][CH:15]=[CH:8][CH:9]=1
Reactant: COc1cc(C=O)cc(F)c1OC
Reactant: C1CCOC1
Reactant: [Li]CCCC
Agent: [PH4+]
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: C(=C\c1ccccc1)\c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 34 %

Procedure:
To a mixture of phosphonium salt 6 (4.7 g, 6.5 mmol) and tetrahydrofuran (25 ml, cooled to −78° C.) was added n-BuLi (2.6 mL, 2.5 M, 6.5 mmol, over 5 minutes), followed by stirring for one hour. Next, 3-fluoro-4,5-dimethoxybenzaldehyde (1 g. 5.4 mmol) in tetrahydrofuran (10 ml) was added (dropwise) over 30 minutes. The mixture was allowed to warm to room temperature, and stirring continued for 16 hours. The reaction was terminated by the addition of water (50 mL), the product was extracted with ethyl acetate, solvents were removed in vacuo, and the residue (1:1 E/Z, 75% yield) obtained was subjected to flash chromatography on silica gel using hexane-ethyl acetate (9:1) as eluent to afford Z-stilbene 7a (1 g, 34%) as a clear oil; 1H-NMR (300 MHz, CDCl3) δ 1.07 (s, 9H), 3.46 (s, 3H), 3.65 (s, 3H), 3.90 (s, 3H), 6.24 (d, 1H, J=12 Hz), 6.33 (d, 1H, J=12 Hz), 6.56 (m, 2H), 6.72 (m, 3H), 7.35 (m, 6H), 7.70 (m, 4H); and 13C NMR (75 MHz, CDCl3) δ 19.75, 26.65, 55.07, 55.99, 61.43, 108.26, 108.28, 109.40, 109.55, 111.74, 120.83, 122.42, 127.36, 127.46, 127.48, 127.70, 129.37, 129.50, 129.63, 130.32, 132.59, 132.66, 133.57, 134.77, 135.27, 135.83, 135.95, 144.74, 149.88, 152.91, 152.95, 154.59, 156.53; HRMS (calcd for C33H36FO4Si) [M+H]+ 543.2368, found 543.2372.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:18](Br)[CH:19]=[CH2:20]>CC(C)=O>[CH2:20]([O:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:10][CH:11]=1)[CH:19]=[CH2:18]
Reactant: C=CCBr
Reactant: COC(=O)c1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: C=CCOc1ccc(C(=O)OC)cc1
Temperature: 25 °C
Yield: 84.6 %

Procedure:
A 2 L flask was equipped with a mechanical stirrer, a reflux condenser and a stopper, then charged with 50.05 g (0.329 mol) of methyl 4-hydroxybenzoate, 960 mL of acetone, 22.50 g (1.625 mol) of anhydrous potassium carbonate, 80.5 mL (112.6 g, 0.932 mol) of allyl bromide and the mixture was stirred and refluxed for 14 hours. The mixture was cooled to room temperature, filtered and concentrated to an oil. The residual oil was purified by distillation (97° C. @ 0.03 mm Hg) to afford 53.52 g (86%) of the title compound.
Reaction SMILES: [CH3:1][OH:2].[C:3]([CH2:5][CH:6]([CH3:11])[C:7]([O:9][CH3:10])=[O:8])#N.[OH2:12]>CCOCC>[CH3:11][CH:6]([CH2:5][C:3]([O:2][CH3:1])=[O:12])[C:7]([O:9][CH3:10])=[O:8]
Reactant: COC(=O)C(C)CC#N
Reactant: O
Reactant: CO
Solvent: CCOCC
Product: COC(=O)CC(C)C(=O)OC

Procedure:
The procedure in Example 1 was repeated to proceed with reaction except that in the second step of esterification, methanol in an amount by weight of 2.6 times that of the methyl 3-cyanoisobutyrate was intermittantly added dropwise to the content in the flask at 100° C. at atmospheric pressure under the reflux of methanol over a period of 5 hours; then at least 90% of water which was formed by the by-production of ether was removed outside the reaction system together with methanol; and additional methanol in an amount of 2.6 times that of the methyl 3-cyanoisobutyrate was intermittantly added dropwise to the content in the flask at 100° C. at atmospheric pressure under the reflux of methoanol over a period of 5 hours. As a result, dimethyl methylsuccinate was obtained at a yield of 97.6 mol % based on the fed methyl 3-cyanoisobutyrate, and by-production of dimethyl ether was at most 1 mol % based on the dimethyl methylsuccinate thus formed.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]1[NH:12][C:13]([CH2:15][CH3:16])=[N:14][C:6]1=[N:5]2.[Cl:17][C:18]([SH:21])([Cl:20])[Cl:19].O1CCCC1.C(N(CC)CC)C>O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]1[N:12]([S:21][C:18]([Cl:20])([Cl:19])[Cl:17])[C:13]([CH2:15][CH3:16])=[N:14][C:6]1=[N:5]2
Reactant: CCc1nc2nc3cc(Cl)ccc3nc2[nH]1
Reactant: SC(Cl)(Cl)Cl
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCc1nc2nc3cc(Cl)ccc3nc2n1SC(Cl)(Cl)Cl

Procedure:
Two parts of 6-chloro-2-ethyl-1H-imidazo[4,5-b]quinoxaline was combined with two parts of perchloromethyl mercaptan in sixty parts of tetrahydrofuran. One part of triethylamine was added slowly dropwise at 30° over a one-hour period. The mixture was poured into water and crude product was collected. The material was recrystallized from a chloroform:hexane mixture to give 1 part of 6-chloro-2-ethyl-1-trichloromethanesulfenyl-1H-imidazo[4,5-b]quinoxaline, m.p. 250° (dec.).